(Ivanhoe Newswire)-- Children with multiple hereditary exostoses (MHE), suffer from multiple growths in their bones that cause pain and disfigurement. However aside from the physical impairments, parents also notice that their children with MHE also experience autism-like social problems.
With the encouragement of parents, researchers at Sanford-Burnham Medical Research Institute are able to uncover the link between autism and MHE by using a mouse model of MHE to investigate cognitive function. They found that mice with a genetic defect that models human MHE show symptoms that meet the three defining characteristics of autism.
"There is growing evidence that many autistic people have related genetic defects, or defects that are exacerbated by this one," Yu Yamaguchi, M.D., Ph.D., professor in the Sanford Children's Health Research Center at Sanford-Burnham." Yamaguchi led this study, along with colleagues Fumitoshi Irie, Ph.D. and Hedieh Badie-Mahdavi, Ph.D., was quoted as saying.
In humans, MHE is caused by a mutation in one of two genes, Ext1 or Ext2. Together, these genes encode an enzyme necessary to produce heparan sulfate—a long sugar chain that helps bone cells grow and proliferate. In this study, Yamaguchi and his team used mice that lack the Ext1 gene in just a certain type of neuron to understand the mechanism of social problems in MHE patients.
The mice were tested for the three defining characteristics of autism: social impairment, language deficits, and repetitive behavior. The team found that the mutant mice were less social than normal mice. They also exhibited language deficiencies, as determined using ultrasound vocalization measurements, a well-characterized substitute for mouse language. Lastly, Yamaguchi's team took at look at repetitive behaviors in these mice. Using a board covered with holes, they observed that normal mice will poke their noses in many holes at random, while the mutant mice poke their noses in the same hole again and again.
This information clearly demonstrates what the parents of children with MHE have always suspected—the disease affects more than just bones. The genetic defect that causes skeletal deformities also causes social and cognitive problems.
Not all autistic children have MHE, nor are all MHE children autistic. But, according to Yamaguchi, there is evidence that some people who are autistic might have similar defects in heparan sulfate. This is the sugar chain that's defective in MHE, where it causes bone deformities and social deficits.
"There are a few studies that compared the genomes of healthy and autistic people and they revealed differences in some heparan sulfate-related genes," Yamaguchi was quoted as saying.
There are most likely many different genetic abnormalities that can lead to autism in the general population. This study and others now indicate that for some, the condition could be caused by mutations in genes encoding enzymes and proteins involved in making heparan sulfate.
Yamaguchi's team is now comparing DNA from autistic and non-autistic volunteers to look for mutations in heparan sulfate genes. So far the initial results have been encouraging.
"I can't emphasize enough how much it helped that the parents of kids with MHE got involved and supported this research," Yamaguchi said. "As parents, they noticed their kids had social problems that gave them challenges at school. School officials and other people didn't take these observations seriously—they usually just waved off the problems, assuming that the kids' bone deformities just make them shy. This latest research doesn't solve any bone issues for MHE patients, but it does help support what the parents always knew—these children need special care."
SOURCE: Proceedings of the National Academy of Sciences, March 2012.